The primary goal in the treatment of wounds is to achieve wound closure. Many wounds routinely heal by a process which comprises six major components: i) inflammation, ii) fibroblast proliferation, iii) blood vessel proliferation, iv) connective tissue synthesis v) epithelialization, and vi) wound contraction. Wound healing is impaired when these components, either individually or as a whole, do not function properly. Thus, therapeutics that provide a benefit to any of these components provide a benefit to the wound healing process.
During wound healing, cells, including fibroblasts, migrate into the wound area. These cells form stress fibers and focal adhesions that serve to help close the wound during the wound contraction step. While wound contraction is an essential component of wound healing, the development of scar contractures in tissues and organs disrupts normal organ integrity and produces functional deformities. Limiting wound contraction during the wound healing process allows the surrounding tissue more time to regenerate and heal with reduced scarring. Thus, compounds that limit wound contraction can be used to reduce scar formation that accompanies wound healing.
It has recently been determined that cyclic nucleotide-dependent relaxation of vascular smooth muscle is associated with an increase in the phosphorylation of the small heat shock related protein 20 (“HSP20”). HSP20 is highly and constitutively expressed in muscle tissues and can be phosphorylated in vitro by cGMP-dependent protein kinase. HSP20 has been shown to associate with actin and α-actinin, a focal adhesion protein. Activation of cyclic nucleotide dependent signaling pathways also leads to a decrease in the association of HSP20 with α-actinin, suggesting that HSP20 may lead to relaxation of vascular smooth muscle through a dynamic association with cytoskeletal proteins.
However, the role of HSP20 and peptides derived therefrom in modulation of wound healing and scar formation responses is not known.